Polaron stability in oligoacene crystals

The polaron stability in organic molecular crystals is theoretically investigated in the scope of a two-dimensional Holstein–Peierls model that includes lattice relaxation. Particularly, the investigation is focused on designing a model Hamiltonian that can address properly the polaron properties in different model oligoacene crystals. The findings showed that a suitable choice for a set of parameters can play the role of distinguishing the model crystals and, consequently, different properties related to the polaron stability in these systems are observed. Importantly, the usefulness of this model is stressed by investigating the electronic localization of the polaron, which provides a deeper understanding into the properties associated with the polaron stability in oligoacene crystals.     

合成生物学伦理、法律与社会问题探讨

合成生物学是以基因组学、系统生物学知识和分子生物学技术为基础,综合了科学与工程的一门新兴交叉学科。它使生命科学和生物技术研发进入了以人工设计、合成自然界中原本不曾出现的人造生命体系,以及对这些人工体系进行体内、体外优化,或利用这些人造生命体系研究自然生命规律为目标的新时代。然而,合成生物学研究在迅速发展、表现出巨大潜力和应用前景的同时,也引发了社会各界对相关社会、伦理、安全,以及知识产权等问题的重视与讨论。就世界各国针对合成生命对传统意义上生命概念的挑战、合成生物学产品存在的潜在风险危害、合成生物学研究的风险评估与监管等问题进行回顾综述和相关探讨。     

Applying the PDR principle to AIDS

The principle of pathogen-derived resistance (the PDR principle) has been put forward as a broadly-applicable conceptual tool for use in designing genes which will confer resistance to pathogens. This paper reveals an example of how the PDR principle may be applied in the field of human medicine. Specifically it is shown how the PDR principle can be employed in designing a series of genes which should be capable of protecting human blood cells from the retrovirus causing the AIDS disease. Prospects are discussed for using such genes in gene therapy treatment of people infected with this virus.     

Towards mixed sequence recognition by triple helix formation

The formation of intermolecular DNA triple helices offers the possibility of designing compounds with extensive sequence recognition properties which may be useful as antigene agents or tools in molecular biology. One major limitation of this approach is that these structures are generally restricted to homo-purine. homopyrimidine target sites. This review describes the strategies that have been employed to overcome this drawback and outlines the potential for triplex formation at mixed sequence DNA targets.     

amiRNA分子设计及其离体合成策略

详细介绍了基于WMD3 (Web MicroRNA Designer 3) 软件平台的amiRNA (artificial microRNA)分子自动设计方法及其离体合成策略。应用网络在线设计时,只需输入目的基因靶序列相关信息后便可获得候选amiRNA。根据选定的最佳amiRNA,可得到四条含有amiRNA以及载体中miRNA 两侧序列的寡聚核苷酸序列。重叠延伸PCR合成策略可以以这四条序列以及根据质粒模板设计的A、B两段序列作为引物,扩增出目标amiRNA。同样尿嘧啶切除的策略也可合成amiRNA,但这些引物序列需做适当调整变动。此外,本文还介绍了基于特异引物退火的amiRNA合成策略,该策略可保证amiRNA分子能够一步PCR合成,合成后的amiRNA表达盒可通过合适的限制性位点被克隆至目的载体中的相应位点。可以预见,这种amiRNA分子设计的科学性与合成策略的精确性将会使amiRNAi技术在生物基因功能分析中发挥更加重要的作用,对生命科学研究产生深远的影响。     

RNAsoft: A suite of RNA secondary structure prediction and design software tools

DNA and RNA strands are employed in novel ways in the construction of nanostructures, as molecular tags in libraries of polymers and in therapeutics. New software tools for prediction and design of molecular structure will be needed in these applications. The RNAsoft suite of programs provides tools for predicting the secondary structure of a pair of DNA or RNA molecules, testing that combinatorial tag sets of DNA and RNA molecules have no unwanted secondary structure and designing RNA strands that fold to a given input secondary structure. The tools are based on standard thermodynamic models of RNA secondary structure formation. RNAsoft can be found online at http://www.RNAsoft.ca.     

Molecular approaches for AM fungal community ecology: A primer

Molecular techniques are no longer optional for ecologists interested in arbuscular mycorrhizal (AM) communities. Understanding the role of these soil fungi in natural systems requires knowledge of their abundance and identity but this is impossible to achieve without a molecular approach. Adapting molecular tools to AM fungi can be challenging because of the unique biology of the fungi. Moreover, many recruits in the field of mycorrhizal ecology have little or no experience with molecular biology. Here, we outline a conceptual framework for designing robust ecological experiments with AM fungi using molecular approaches.     

Design of high-density antibody microarrays for disease proteomics: Key technological issues

Antibody-based microarray is a novel proteomic technology setting a new standard for molecular profiling of non-fractionated complex proteomes. The first generation of antibody microarrays has already demonstrated its potential for generating detailed protein expression profiles, or protein atlases, of human body fluids in health and disease, paving the way for new discoveries within the field of disease proteomics. The process of designing highly miniaturized, high-density and high-performing antibody microarray set-ups have, however, proven to be challenging. In this mini-review we discuss key technological issues that must be addressed in a cross-disciplinary manner before true global proteome analysis can be performed using antibody microarrays.     

Molecular docking and 3D-QSAR studies of Yersinia protein tyrosine phosphatase YopH inhibitors

Three-dimensional quantitative structure-activity relationship (QSAR) studies were conducted on two classes of recently explored compounds with known YopH inhibitory activities. Docking studies were employed to position the inhibitors into the YopH active site to determine the probable binding conformation. Good correlations between the predicated binding free energies and the inhibitory activities were found for two subsets of phosphate mimetics: alpha-ketocarboxylic acid and squaric acid (R2=0.70 and 0.68, respectively). The docking results also provided a reliable conformational alignment scheme for 3D-QSAR modeling. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed based on the docking conformations, giving q2 of 0.734 and 0.754 for CoMFA and CoMSIA models, respectively. The 3D-QSAR models were significantly improved after removal of an outlier (q2=0.829 for CoMFA and q2=0.837 for CoMSIA). The predictive ability of the models was validated using a set of compounds that were not included in the training set. Mapping the 3D-QSAR models to the active site of YopH provides new insight into the protein-inhibitor interactions for this enzyme. These results should be applicable to the prediction of the activities of new YopH inhibitors, as well as providing structural implications for designing potent and selective YopH inhibitors as antiplague agents.     

Structural studies on ligand–DNA systems: A robust approach in drug design

Molecular docking, molecular mechanics, molecular dynamics and relaxation matrix simulation protocols have been extensively used to generate the structural details of ligand-receptor complexes in order to understand the binding interactions between the two entities. Experimental methods like NMR spectroscopy and X-ray crystallography are known to provide structural information about ligand-receptor complexes. In addition, fluorescence spectroscopy, circular dichroism (CD) spectroscopy and molecular docking have also been utilized to decode the phenomenon of the ligand-DNA interactions, with good correlation between experimental and computational results. The DNA binding affinity was demonstrated by analysing fluorescence spectral data. Structural rigidity of DNA upon ligand binding was identified by CD spectroscopy. Docking is carried out using the DNA-Dock program which results in the binding affinity data along with structural information like interatomic distances and H-bonding, etc. The complete structural analyses of various drug-DNA complexes have afforded results that indicate a specific DNA binding pattern of these ligands. It also exhibited that certain structural features of ligands can make a ligand to be AT- or GC-specific. It was also demonstrated that changing specificity from AT base pairs to GC base pairs further improved the DNA topoisomerase inhibiting activity in certain ligands. Thus, a specific molecular recognition signature encrypted in the structure of ligand can be decoded and can be effectively employed in designing more potent antiviral and antitumour agents.     

Oligonucleotides and derivatives as gene-specific control agents

The current achievement of genome sequence projects of a dozen eukaryote organisms (including human genome) and the development of functional genomics are providing the basic knowledge required to utilize gene-specific reagents for both basic understanding of cell physiology and therapeutical development. The field of chemical genomics has the ambitious goal of designing molecules that could act selectively on every single gene or gene product in a cell and in vivo. The progress in oligonucleotide-based approaches will be the topic of this review, however, other nucleic acid- and SELEX-based approaches as well as high sequence-specific low molecular weight DNA-specific ligands will also be discussed.     

质体样细胞器APICOPLAST起源的分子证据评述

顶复合器门的原生动物(Apicomplexan protozoa)含有一个高度退化的质体样(pIastid-like)细胞器,定名为apicoplast.Apicoplast的进化起源是一个长期激烈争论的问题,尽管使用了多种分子技术,但尚未取得一致的结论,以致成为质体起源研究的典型案例.文章评述了apicoplast起源研究的分子证据,分析了新的分子证据的可能来源,为进一步研究提供线索.     

质体样细胞器APICOPLAST起源的分子证据评述

顶复合器门的原生动物（Apicomplexan protozoa）含有一个高度退化的质体样（plastid-like）细胞器,定名为apicoplast。Apicoplast的进化起源是一个长期激烈争论的问题,尽管使用了多种分子技术,但尚未取得一致的结论,以致成为质体起源研究的典型案例。文章评述了apicoplast起源研究的分子证据,分析了新的分子证据的可能来源,为进一步研究提供线索。     

Insight into the Oseltamivir Resistance R292K Mutation in H5N1 Influenza Virus: A Molecular Docking and Molecular Dynamics Approach

H5N1 is a subtype of the influenza A virus that can cause disease in humans and many other animal species. Oseltamivir (Tamiflu) is a potent and selective antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase (NA), a flu protein responsible for the release and spread of the progeny virions. However, oseltamivir resistance has become a critical problem. In particular, influenza strains with a R292K NA mutation are highly resistant to the oseltamivir. Though the biological functions of the mutations have previously been characterized, the structural basis behind the reduced catalytic activity and reduced protein level is not clear. In this study, molecular docking and molecular dynamics (MD) approach were employed to investigate the structural and dynamical effects throughout the protein structure and specifically, at the drug-binding pocket. Furthermore, potential of mean force was analyzed using explicit solvent MD simulations with the umbrella sampling method to explore the free energy of binding. It is believed that this study provides valuable guidance for the resistance management of oseltamivir and designing of more potent antiviral inhibitor.     

DNA based iPBS-retrotransposon markers for investigating the population structure of pea (Pisum sativum) germplasm from Turkey

Retrotransposons have been highly studied in monocots; however retrotransposon diversity in dicot crops has not been well documented. Our objective was to assess the diversity harbored by field pea landraces using retrotranposon markers. In this research, molecular characterization of 104 landraces and 34 field pea breeding lines was assessed using newly developed iPBS-retrotransposon markers. The 12 iPBS-retrotransposon primers generated a total 106 scorable bands, and 81 of these were found to be polymorphic (76.4%), with an average of 6.75 polymorphic fragments per primer. Polymorphism information content (PIC) ranged from 0.33 to 0.84 with an average of 0.61. It was evident that field pea landraces from the same geographical region were often placed in different groups in the neighbor joining analysis, indicating that grouping based on genetic parameters was not closely related to the geographical origin. The population structure was determined by using STRUCTURE software, and three populations at K = 3 and five populations at K = 5 were identified among landraces. The plentiful diversity present in Turkish field pea landraces could be used as genetic resource in designing breeding program, and may also contribute to worldwide pea breeding programs. Our data also suggested a role of iPBS-retrotransposons as ‘a universal marker’ for molecular characterization of pea germplasm.     

Determination of molecular order in supported lipid membranes by internal reflection Fourier transform infrared spectroscopy.

When polarized internal reflection infrared spectroscopy is used to determine molecular order in supported lipid membranes, the results are critically dependent on the accuracy of assumptions made about the evanescent electric field amplitudes in the membrane. In this work, we examine several expressions used for calculating evanescent electric field amplitudes in supported lipid monolayers and bilayers, and test their validity by measuring the infrared dichroism of poly-gamma-benzyl-L-glutamate and poly-beta-benzyl-L-aspartate under conditions in which their molecular order is known. Our results indicate that treating such systems as a simple single interface between two semi-infinite bulk phases is more accurate than the commonly employed thin-film approximation. This implies that earlier conclusions about molecular order in supported lipid membranes may require substantial revision.     

Genetics of preneoplasia: lessons from lung cancer

From biological, histopathologic, and clinical perspectives, lung cancer is a highly complex neoplasm probably having multiple preneoplastic pathways. The sequence of histopathologic changes in the bronchial mucosa that precedes the development of squamous carcinomas of the lung has been identified. For the other major forms of lung cancer, however, such sequences have been poorly documented. This review summarizes the current knowledge regarding the molecular and histopathologic pathogenesis of lung cancer and discusses the complexity of identifying novel molecular mechanisms involved in the development of the lung premalignant disease, and their relevance to the development of new strategies for early detection and chemoprevention. Although our current knowledge of the molecular pathogenesis of lung cancer is still meager, work over the last decade has taught several important lessons about the molecular pathogenesis of this tumor, including the following: a) Better characterization of the high-risk population is needed. b) There are several histopathologic and molecular pathways associated with the development of the major types of non-small cell lung cancer. c) Although there is a field effect phenomenon for lung preneoplastic lesions, recent data suggest that there are at least two distinct lung airway compartments (central and peripheral) for lung cancer pathogenesis. d) Inflammation may play an important role in lung cancer development and could be an important component of the field effect phenomenon. e) For lung adenocarcinoma, at least two pathways (smoking-related and nonsmoking-related) have been identified. f) Finally, the identification of deregulated molecular signaling pathways in lung cancer preneoplasias may provide a rationale for designing novel strategies for early detection and targeted chemoprevention of lung cancer.     

Oligonucleotides and Derivatives as Gene-Specific Control Agents

Abstract

The current achievement of genome sequence projects of a dozen eukaryote organisms (including human genome) and the development of functional genomics are providing the basic knowledge required to utilize gene-specific reagents for both basic understanding of cell physiology and therapeutical development. The field of chemical genomics has the ambitious goal of designing molecules that could act selectively on every single gene or gene product in a cell and in vivo. The progress in oligonucleotide-based approaches will be the topic of this review, however, other nucleic acid- and SELEX-based approaches as well as high sequence-specific low molecular weight DNA-specific ligands will also be discussed.     

Concerted action of the FasL/Fas and perforin/granzyme A and B pathways is mandatory for the development of early viral hepatitis but not for recovery from viral infection

Cytotoxic T lymphocytes (CTL) play a major role in the recovery from primary viral infections and the accompanying tissue injuries. However, it is unclear to what extent the two main cytolytic pathways, perforin-granzyme A and B exocytosis and Fas ligand (FasL)-Fas interaction, contribute to these processes. Here we have employed mouse strains with either spontaneous mutations or targeted gene defects in one or more components of either of the two cytolytic pathways to analyze the molecular basis of viral clearance and induction of hepatitis during lymphocytic choriomeningitis virus infection. Our results reveal that viral clearance is solely dependent on perforin but that virus-induced liver damage only occurs when both the FasL/Fas and the perforin pathways, including granzymes A and B, are simultaneously activated. The finding that development of hepatitis but not viral clearance is dependent on the concomitant activation of FasL-Fas and perforin-granzymes may be helpful in designing novel strategies to prevent hepatic failures during viral infections.